Dr. Gleeson received his M.D. from the University of Chicago, residency in pediatrics and neurology at Harvard Medical School and Children’s Hospital Boston and then postdoctoral research fellowship in neurobiology and genetics at Harvard Medical School. He has appointments at the University of California San Diego, Rady Children’s Hospital San Diego, and The Rockefeller University. He is an Investigator with the Howard Hughes Medical Institute, an Investigator with the Simons Foundation for Autism Research, and a member of the US National Academy of Science Institute of Medicine.
His research is focused on genetic brain diseases, with the goal of discovering genetic causes of disease, uncovering mechanisms and developing new treatments. The lab has leveraged the largest cohort of families with autism due to recessive neurodevelopmental and neurodegenerative disease using next-generation sequencing. With over 6000 patients sequenced to date, the lab has uncovered causes for over 100 genetic diseases along a spectrum of epilepsy, autism, intellectual disability, neurodegenerative conditions. Mutations are modeled using biochemistry, cell culture, IPSCs, as well as mouse and zebrafish models.
The work has uncovered several pediatric brain diseases that were previously considered untreatable to have obvious points of treatment. Gleeson identified the Doublecortin gene mutated in lissencephaly. He described mutations in the BCKDK gene in patients with autism and epilepsy that predict that should respond to simple nutritional supplementation of branched chain amino acids, and recent trials have been successful. They described mutations in the MTOR, AKT3, PIK3CA genes in patients with hemimegalencephaly that predict they should respond to medications inhibiting the mTOR pathway. He described mutations in the AMPD2 gene in patients with a form of neurodegeneration that predict that they should respond to simple nutritional supplementation.